This invention generally pertains to piperazinyl- and piperidinyl-cyclohexanol compounds having anxiolytic and other psychotropic, bioaffecting properties and to their preparation and use. In some preferred embodiments, the invention is concerned with 1,4-disubstituted piperazine or piperidine derivatives wherein the 4-substituent is benzyl or substituted benzyl, and the 1-substituent is 4-aryl-4-hydroxycyclohexyl or 4-aryl-4-alkoxycyclohexyl moiety. These compounds and others structurally related thereto possess a unique serotonergic profile that makes them useful in the treatment of anxiety. Caprathe et al disclosed a series of piperazinyl-cyclohexanol compounds characterized by structural Formula A in U.S. Pat. No. 4,957,921. Formula A is: ##STR2## wherein n is 0 to 4 and Ar and Ar' are aryl or heterocyclic rings.
As can be seen, these earlier compounds are chemically distinguishable from the instant compounds on the basis of their chemical structures because they are aryl- or heteroaryl-piperazines, whereas the instant compounds are benzyl- or heteroarylmethyl-piperazines (when, in Formula I below, Y.dbd.N) or piperidines (when, in Formula I below, Y.dbd.CH). Additionally, these earlier compounds are biologically distinguishable from the instant compounds, since they possess dopaminergic properties, which are associated with undesirable side effects including Parkinsonism and extrapyramidal side effects such as catalepsy. Contrastingly, the instant compounds are serotonergic agents devoid of dopaminergic properties and the movement disorders often associated therewith.
Caprathe et al disclosed a series of piperazinyl-cyclohexene compounds characterized by structural formula B in U.S. Pat. No. 4,975,445. Formula B is: ##STR3## wherein R.sup.1 is an aryl or heterocyclic ring, m is 0-2 and n is 0-4. Likewise, these compounds are structurally and biologically distinguishable from the instant compounds. Chemically, the reference compounds are aryl-piperazines, while the instant compounds are benzyl- or heteroarylmethyl-piperazines. Biologically, their dopaminergic properties distinguish them from applicants' compounds, which have serotonergic activity. Accordingly, the movement disorders associated with dopaminergic agents are avoided when the instant compounds are administered.